Stent

ABSTRACT

A stent is disclosed that has an elongated body having a proximal end, a distal end, at least one open spiral channel formed on the exterior surface of the body to provide fluid communication between the proximal end and the distal end. The stent also has a central lumen open at the proximal and distal ends of the stent for the passage of a guide wire. A method for using the stent and a kit containing the stent are also disclosed.

This application is a Continuation-In-Part of U.S. application Ser. No.14/841,196, filed Aug. 31, 2015, which is a Continuation of U.S.application Ser. No. 12/539,314, filed Aug. 11, 2009, which is aContinuation-In-Part of U.S. application Ser. No. 12/417,122, filed onApr. 2, 2009, now U.S. Pat. No. 8,246,691. The entirety of theaforementioned applications is incorporated herein by reference.

FIELD

The present application generally relates to medical devices and, inparticular, to a stent with one or more open channels formed on itsexterior surface.

BACKGROUND

In medical terms, a stent is a man-made “tube” inserted into a naturalpassage or conduit in the body to prevent, or counteract, adisease-induced, localized flow constriction. The term may also refer toa tube used to temporarily hold such a natural conduit open to allowaccess for surgery. Stents include vascular and non-vascular stents.Vascular stents are designed for applications in the vascular system,such as arteries and veins. Non-vascular stents are used in other bodylumens such as biliary, colorectal, esophageal, ureteral and urethraltract, and upper airway.

Stents are available in permanent and temporary varieties. Stentduration is heavily influenced by the construction material. Forexample, metal stents typically have a much longer use life than plasticstents. The stent body typically has a central lumen that allows bloodor other body fluid to flow through the stent. A common problem with thecurrent stents is that they routinely migrate and clog, thus requiringadditional procedures for extraction and/or replacement. There exists aneed for improved stents that are easy to make and safe to use.

In chronic pancreatitis, a fibrotic duct stricture is a commoncomplication and a therapeutic challenge. Drainage of an obstructed ductbecomes mandatory because the intraductal pressure created by thestricture causes severe pain. At present, these fibrotic strictures areendoscopically treated by the sequential placement of multiple plasticstents for a period of six to twelve months with stent exchangesapproximately every three months. These procedures are expensive and canincrease risks for patients suffering from comorbidities.

The present application provides a stent device having superiorproperties for supporting a vessel, duct or lumen and optimizing theflow of bodily fluids through the use of external longitudinal channelsthat spiral around the device.

SUMMARY

One aspect of the present application relates to a stent comprising anelongated body having a proximal end, a distal end, at least one openspiral channel formed on the exterior surface of said body to providefluid communication between said proximal end and said distal end, and acentral lumen open at the proximal and distal ends of the stent for thepassage of a guide wire.

Another aspect of the present application relates to a stent comprisingan elongated body composed of a bioabsorbable polymer and having aproximal end, a distal end, at least one open spiral channel formed onthe exterior surface of said body to provide fluid communication betweensaid proximal end and said distal end, wherein said at least one openspiral channel has a rotation rate of at least 1 twist per inch, and acentral lumen open at the proximal and distal ends of the stent for thepassage of a guide wire.

Still another aspect of the present application relates to a stentcomprising an elongated body having a proximal end, a distal end, atleast one open spiral channel formed on the exterior surface of saidbody to provide fluid communication between said proximal end and saiddistal end, wherein said at least one open spiral channel has a rotationrate of between about 1.5 and 3.5 twists per inch, and a central lumenopen at the proximal and distal ends of the stent for the passage of aguide wire.

Yet another aspect of the present application relates to a stentcomprising an elongated body composed of a bioabsorbable polymer andhaving a proximal end, a distal end, a pair of open spiral channelsformed on the exterior surface of said body to provide fluidcommunication between said proximal end and said distal end, whereinsaid spiral channels have a rotation rate of at least about 1 twist perinch, and a central lumen open at the proximal and distal ends of thestent for the passage of a guide wire.

Another aspect of the present application relates to a method ofemplacing a stent in a subject in need thereof, comprising: establishingan entry portal into a vessel, duct or lumen contiguous with a targetsite for stent placement, advancing a guide wire through the entryportal and said vessel, duct or lumen contiguous to said target site,and advancing the stent along said guide wire to the target site. Thestent comprises an elongated body having a proximal end, a distal end,at least one open spiral channel formed on the exterior surface of saidbody to provide fluid communication between said proximal end and saiddistal end and a central lumen open at the proximal and distal ends ofthe stent for the passage of a guide wire. The method further comprisesthe step of withdrawing the guide wire.

Still another aspect of the present application relates to a kit forstent placement. The kit comprises a stent comprising an elongated bodyhaving a proximal end, a distal end, at least one open spiral channelformed on the exterior surface of said body to provide fluidcommunication between said proximal end and said distal end and acentral lumen open at the proximal and distal ends of the stent for thepassage of a guide wire. The kit also comprises a guide wire.

BRIEF DESCRIPTION OF THE DRAWINGS

The present application can be better understood by reference to thefollowing drawings, wherein like references numerals represent likeelements. The drawings are merely exemplary to illustrate certainfeatures that may be used singularly or in combination with otherfeatures and the present application should not be limited to theembodiments shown.

FIG. 1A is a diagram showing an embodiment of the stent of the presentapplication. FIG. 1B is a see-through illustration of FIG. 1A.

FIG. 2 is a diagram showing a stent with a sinusoidal shaped stent body.

FIG. 3 is a diagram showing an assembly of a stent with a guide wire anda pusher tube.

FIGS. 4A and 4B are diagrams showing two engagement mechanisms among thestent, the guide wire and the pusher tube.

FIGS. 5A and 5B show an embodiment of an expandable stent.

FIGS. 6A and 6B show another embodiment of an expandable stent.

FIGS. 7A and 7B show another embodiment of an expandable stent.

FIGS. 8A-8F show various embodiments of an expandable stent.

FIGS. 9A-9C show several embodiments of a stent with an outer frame.

FIG. 10 shows another embodiment of a stent with sinusoidal channels ofvarying pitches.

FIGS. 11A-11B shows another embodiment of a stent of the presentapplication.

FIG. 12 shows another embodiment of a stent of the present application.

FIG. 13 shows the cross section of an embodiment of a stent of thepresent application.

FIG. 14 shows the cross section of another embodiment of a stent of thepresent application.

FIG. 15 shows another embodiment of a stent of the present application.

FIG. 16 shows another embodiment of a stent of the present application.

FIG. 17 shows another embodiment of a stent of the present application.

FIG. 18 shows another embodiment of a stent of the present application.

FIGS. 19A-E show another embodiment of a stent of the presentapplication.

FIGS. 20A-D show another embodiment of a stent of the presentapplication.

FIGS. 21A-H show another embodiment of a stent of the presentapplication.

FIGS. 22A-B show an alternative feature for the embodiments of FIGS.19A-21-H.

DETAILED DESCRIPTION

The practice of the subject matter of the present application willemploy, unless otherwise indicated, conventional medical devices andmethods within the skill of the art. Such techniques are explained fullyin the literature. All publications, patents and patent applicationscited herein, whether supra or infra, are hereby incorporated byreference in their entirety.

One aspect of the present application relates to a stent that containsan elongated stent body having a proximal end, a distal end, and atleast one open channel formed on the exterior surface of the elongatedstent body to provide fluid communication from the proximal end to thedistal end of the stent.

As used herein, the term “stent” refers to a device which is implantedwithin a bodily lumen to hold open the lumen or to reinforce a smallsegment of the lumen. Stents can be used for treating obstructedvessels, biliary ducts, pancreatic ducts, ureters, or other obstructedlumens, fractured canals, bones with hollow centers and/or fordelivering various drugs through controlled release to the particularlumen of interest.

The open channel should be large enough to allow unobstructed or normalflow of various body fluids such as blood, bile or urine or otherluminal material/liquids on the outer aspect of the stent. The openchannel may have a cross section area that is of any shape or depth. Thechannel could be V shapes, U shaped, or with a rising or falling pitch,of an even depth or one that is of varying widths, depths, varying andcircumferential rotations changing at various points over the length ofthe device. The channel can be a straight channel or a spiral channel.Multiple channels may be formed on the exterior surface or the innersurface of the elongated stent body. The channel(s) may also be designedwith a geometry that would help the stent to remain in place.

The shape, length and diameter of the stent body are applicationdependent. The elongated stent body can be straight or curved or in theshape of multiply connected and angulated curves. Each type of stent isdesigned to fit within a specific part of the anatomy. Therefore, theshape, length, and diameter of stents differ by type to accommodate andsupport different sized lumens and different clinical needs. Forexample, each major stent application, such as vascular, pancreatic,ureteral, or metacarpal canal, other hollow bone structures and otherstent, requires a different diameter and shape to enable placement, toremain in place after placement, to stabilize and support the anatomy itis placed in, and to allow conformance to the normal anatomy. As usedherein, the diameter of a stent refers to the width across the shaft ofthe stent body, which is also referred to as the “major diameter.” Inone embodiment, the stent has a uniform diameter. In another embodiment,the stent has a variable diameter. In one embodiment, the diameter atthe distal end is smaller than the diameter at the proximal end. Inanother embodiment, the diameter at the proximal end is smaller than thediameter at the distal end. In yet another embodiment, the diameters atthe distal end and the proximal end are both smaller than the diameterat the middle section of the stent.

The stent body may further include a center lumen to accommodate a guidewire. This center lumen may provide additionally flow throughput afterthe removal of guide wire.

One aspect of the present application relates to a stent comprising anelongated body having a proximal end, a distal end, at least one openspiral channel formed on the exterior surface of said body to providefluid communication between said proximal end and said distal end, and acentral lumen open at the proximal and distal ends of the stent for thepassage of a guide wire.

In some embodiments, the body is composed of a bioabsorbable polymer.

In other embodiments, the at least one open spiral channel has arotation rate of between about 1.5 and 2.5 twists per inch.

In still other embodiments, the at least one open spiral channel has arotation rate of at least about 2 twists per inch.

In some embodiments, the stent comprises two open spiral channels formedon the exterior surface of said body. In some further embodiments, thechannels are on opposite sides on the exterior surface of said body.

In some embodiments, the body further comprises an anti-migrationdevice.

In other embodiments, the body further comprises a biological agent. Insome further embodiments, the biological agent is selected from thegroup consisting of chemotherapeutic agents, antimicrobial agents andgene transfer agents.

In particular embodiments, the stent has a pre-implantation diameterD_(pre) and is in situ expandable upon absorption of a body fluid to apost-implantation diameter D_(post), wherein D_(post) is greater thanD_(pre).

In some embodiments, the stent comprises a radio-opaque substance.

Another aspect of the present application relates to a stent comprisingan elongated body composed of a bioabsorbable polymer and having aproximal end, a distal end, at least one open spiral channel formed onthe exterior surface of said body to provide fluid communication betweensaid proximal end and said distal end, wherein said at least one openspiral channel has a rotation rate of at least 1 twist per inch, and acentral lumen open at the proximal and distal ends of the stent for thepassage of a guide wire.

In some embodiments, the bioabsorbable polymer comprises PEG andp-dioxanone.

In other embodiments, the bioabsorbable polymer comprises PPDO.

In still other embodiments, the bioabsorbable polymer comprises PLA,trimethylene carbonate and caprolactone.

In some embodiments, the at least one open spiral channel has a rotationrate of at least about 2 twists per inch.

In particular embodiments, the stent comprises two open spiral channelsformed on the exterior surface of said body. In some furtherembodiments, the channels are on opposite sides on the exterior surfaceof said body.

Still another aspect of the present application relates to a stentcomprising an elongated body having a proximal end, a distal end, atleast one open spiral channel formed on the exterior surface of saidbody to provide fluid communication between said proximal end and saiddistal end, wherein said at least one open spiral channel has a rotationrate of between about 1.5 and 3.5 twists per inch, and a central lumenopen at the proximal and distal ends of the stent for the passage of aguide wire.

In some embodiments, the stent comprises two open spiral channels formedon the exterior surface of said body. In some further embodiments, thechannels are on opposite sides on the exterior surface of said body.

Yet another aspect of the present application relates to a stentcomprising an elongated body composed of a bioabsorbable polymer andhaving a proximal end, a distal end, a pair of open spiral channelsformed on the exterior surface of said body to provide fluidcommunication between said proximal end and said distal end, whereinsaid spiral channels have a rotation rate of at least about 1 twist perinch, and a central lumen open at the proximal and distal ends of thestent for the passage of a guide wire.

In some embodiments, the channels are on opposite sides on the exteriorsurface of said body.

Another aspect of the present application relates to a method ofemplacing a stent in a subject in need thereof, comprising: establishingan entry portal into a vessel, duct or lumen contiguous with a targetsite for stent placement, advancing a guide wire through the entryportal and said vessel, duct or lumen contiguous to said target site,and advancing the stent along said guide wire to the target site. Thestent comprises an elongated body having a proximal end, a distal end,at least one open spiral channel formed on the exterior surface of saidbody to provide fluid communication between said proximal end and saiddistal end and a central lumen open at the proximal and distal ends ofthe stent for the passage of a guide wire. The method further comprisesthe step of withdrawing the guide wire.

Still another aspect of the present application relates to a kit forstent placement. The kit comprises a stent comprising an elongated bodyhaving a proximal end, a distal end, at least one open spiral channelformed on the exterior surface of said body to provide fluidcommunication between said proximal end and said distal end and acentral lumen open at the proximal and distal ends of the stent for thepassage of a guide wire. The kit also comprises a guide wire.

In one embodiment, the stent is naturally formed by braiding multiplefilaments together. In another embodiment, the stent is made with acenter rod/hub/cam having one or more sinusoidal channels runningthrough the exterior surface of the center rod, similar to that of adrill bit.

The stent of the present application can be expandable. In oneembodiment, the stent is of two different diametrical dimensions due toradial deformation of its elastic elements. Before being positioned atthe place of reconstruction, the stent is deformed/compressed/folded soas to minimize its diametrical dimension. Then the stent is placed, inthe deformed state, inside a transporting means by arranging it on aspecial setting bulb. Once the stent has been transported to the placeof reconstruction, the setting bulb is expanded so that the stentdiameter is maximized. In another embodiment, the stent has a pluralityof flexible or foldable channel walls or leaflets extending from thecenter rod/hub/cam. The channel walls or leaflets are kept in a foldedposition during the delivery process and are released only at thetreatment site.

In one embodiment, the stent is delivered to the treatment site in abody lumen with a pusher rod that pushes the stent through a bodychannel into place. The pusher rod travels over a guide wire. The pusherrod is designed in such a way to attach to the ends of the stent toassist with directing the delivery. In one embodiment, the pusher rodinterlocks with the proximal end of the stent in a male/female fashion,much the same way a wrench fits over a nut.

FIG. 1A is a diagram showing an embodiment of the stent of the presentapplication. In this embodiment, stent 100 has an elongated body 10 witha proximal end 12 and a distal end 14. Two sinusoidal channels 16 areformed on the exterior surface of the elongated body 10, extending fromthe proximal end 12 to the distal end 14 in a fashion similar to thegrooves on a drill head. The channels may have beveled edges tofacilitate fluid flow inside the channels. The channels can be ofvarying depths and lengths. The ends of the stent body can be of variousshapes including conical shape. FIG. 1B is a see through drawing of FIG.1A. The two-channel design allows for two channels on the exteriorsurface of the stent to run in parallel from one end to the other or tocriss-cross to allow for increased fluid flow as well as the ability toincrease side branch flow of the main stented channel.

A center lumen 20 allows the stent 100 to slide into the place ofimplantation through a guide wire.

FIG. 2 shows another embodiment of the stent of the present application.In this embodiment, stent 200 has a modified sinusoidial body shape toimprove flexibility, allow for varying flow dynamics, and facilitatecontour and wall adherence to the lumens. The multiple V shaped channels16 allow for the flow of various body fluids. The diameter of theinternal lumen 20 and the outer diameter of the stent body can bechanged based on the need for various luminal dimensions, shapes, flows,and biomechanics. The tapered tip 18 facilitates advancement of thestent inside a body lumen.

FIGS. 13 and 14 show cross-sections of V-shaped channel and channelwalls. The channels can be of varying depths and varying widths tochange the volume and speed of fluid flow. The bottom of the channel canbe rounded or tapered or formed by a direct angle.

The stent of the present application may be implanted with procedureswell known to a person of ordinary skill in the art. Examples of suchprocedures include, but are not limited to, standard percutaneousapproach using a guide wire, endoscopic retrogradecholangiopancreatography (ERCP) placement procedures, and otherradiographic/angiographic procedures. FIG. 3 shows an assembly of astent 200 with a guide wire 24 and a pusher tube 26. FIG. 4 showsseveral engagement mechanisms among the stent 300, the guide wire 24 andthe pusher 26. In FIG. 4A, the pusher tube has several fingers to holdthe stent 300 like a hand or clamp. In FIG. 4B, the pusher 26 interlockswith the stent 300 in a male/female fashion to ensure security ofpositioning and delivery of the stent 300. The interlocking mechanismmay involve a male to female interconnect of various shapes, sizes, ordimensions.

FIGS. 5A and 5B show an embodiment of an expandable stent 500 withcompressible channel walls 50. In a closed state (FIG. 5A), the channelwalls 50 are compressed or twisted against each other to reduce stentdiameter. Once the stent has been transported to the treatment site, thechannel walls are restored to their natural shape (FIG. 5B).

FIGS. 6A and 6B show another embodiment of an expandable stent 600 withfoldable leaflets 60. In an extended state, the thin leaflets 60 allowfor unobstructed flow of body fluid (FIG. 6A). In one embodiment, theleaflets 60 are contoured and aligned in a way to increase the flowspeed of the body fluid or to provide minimal drag. The impedance of theflow volumes and the velocity can be modulated by changing the anglesand contour of the leaflets. Additionally the interconnecting supportscan be thicker at the cam to provide different levels of stability andrigidity for the bracing arms 62, which help support the structure theyare placed in. The bracing arms 62 can be connected at anywhere alongtheir diameter and the change in connection points will have an impactin the rigidity of the support of the lumen, the ability of the deviceto flex with the normal body movement of the lumen, and will change theminimal diameter the device can be collapsed in. The stent 600 mayfurther contain a center lumen 20.

As shown in FIG. 6B, the leaflets 60 may be rotated pivotally (e.g.,clockwise) to collapse into each other to reduce the size of the stentto facilitate implantation. Once in place, the stent may be rotated inan opposite direction (e.g., counter clockwise) to restore to itsextended state. The tip of the stent 600 can be titled or coned orshaped into various configurations to allow for access to different bodylumens. The opened leaflets 60 further have the benefit to preventmigration of the stent 600.

FIGS. 7A and 7B show another embodiment. In this embodiment, theexpandable stent 700 has closed connections around each alternatingleaflet 70 to allow for changes in flexibility, radial force,compression resistance, and absorption. The leaflets 70 have asinusoidal pattern and can be thicker at the attachment to inner cam 72to allow for variations of rigidity. The outer cam 74 prevents tissuegrowth inside the stent body and increases contact area between thestent 700 and inner wall of the body lumen. The thickness of outer cam74 is application dependent. The outer cam 74 may also be beveled. Thestent 700 may have a removal grip attached to the end of center lumen 20to allow for easy removal of the stent 700.

FIG. 7B shows another embodiment of the stent 700. In this embodiment,the leaflets 70 are connected to the cam 72 and can be compress downtowards the cam 74. The leaflets may have a hollow interior so thatfluid may flow through and around the leaflets 70.

In another embodiment, stent 800 contains propeller-like leaflets 80that are thicker at the base where they are attached to the cam or rodportion 82 of the stent 800. The leaflets 80 become thinner at the tip(FIG. 8A). The stent 800 may also have a sinusoidal shape to conform toa body lumen.

The propeller-like stent 800 may be constructed in such a way to allowunidirectional collapse of the leaflets to facilitate ease of passagethrough the working channel of an endoscope, bronchoscope, or throughsome other tubular delivery apparatus or opening by simply rotating thestent in a unidirectional manner and then reversing the technique toopen the stent once it is in place. Additionally, the tip of the stent800 may be shaped to allow for ease of collapse or insertion. FIG. 8Bshows a stent 800 in a collapsed configuration.

FIG. 8C shows another embodiment of the stent 800. In this embodiment,the leaflets 80 can be folded towards the cam or rod portion 82 of thestent body, in a manner similar to that of an umbrella. The leaflets 80can be in any shape, such as round, oval, triangle etc. and will have achange in thickness at the base where the leaflets are connected to thecam 82 to allow you to change ease or rigidity of folding the device andpassing it through and opening or channel. The unidirectional leafletsallow the device to be pushed through an opening and then pulled back tosecure it in place. In another embodiment, the leaflets can be foldedtowards the cam or rod portion of the stent body, in a manner similar tothat of an umbrella, a collapsing tree, or unidirectional ormultidirectional folding leaflets of consistent or varying shapes. FIG.8D shows the stent of FIG. 8C in a collapsed configuration.

In another embodiment, the leaflets 80 of the stent 800 can be foldedtogether by rotating along a common axis. FIGS. 8E and 8F show a stent800 in open and folded configurations, respectively. In one embodiment,the stent 800 has a diameter of 1 cm in open configuration and adiameter of 1 mm in folded configuration. Depending on flowrequirements, the channel 88 may have raps ranging from 5 to 100degrees. In certain embodiments, the channel 88 may have raps of about5-20 degrees, 20-40 degrees, 40-60 degrees, 60-80 degrees or 80-100degrees. In certain embodiments, the channel has a rap of about 5degrees, about 10 degrees, about 20 degrees, about 30 degrees, about 40degrees, about 50 degrees, about 60 degrees, about 70 degrees, about 80degrees, about 90 degrees, or about 100 degrees.

In another embodiment, a device has a portion of the device and stentand its leaflets collapsible so that some portion of the device (e.g.,1%) would have uni-direction leaflets and the remainder would have theopposite facing leaflets or directions such as seen on the differentblades of a saw. In yet another embodiment, the leaflets are alternatingin directions so as to prevent migration of the expanded stent.

Referring now to FIG. 9A an embodiment of stent 900 has a taperedproximal end 901 to allow ease of passage inside a body lumen, an outerframe 902 with a larger diameter to provide stiffness, and a center core903 with a smaller diameter to provide flexibility. The outer frame 902and the center core 903 can be cylindrical or cut with various contoursin the surface to change the flexibility or rigidity of the stent. InFIG. 9B, the stent 900 has an outer frame 902 that forms a coil aroundthe core 903. The stent 900 may further include a center lumen 20. InFIG. 9C, the stent 900 has sinusoidal channel 904 formed on the surfaceof outer frame 902. The channel 904 may have variable depth. The centercore 903 may have various shapes and sizes to adjust the flexibility,stability and rigidity of the stent 900.

In one embodiment, the stent 900 is inserted into the canal of a bonehaving a fracture. In another embodiment, the stent 900 is coated with ahydrogel. The hydrogel expands by absorbing of fluids and improves theconnection and support of the inner wall of the bone canal. In anotherembodiment, the stent 900 is used to attach bone fractures together. Inanother embodiment, the stent 900 is placed through the bone cortex.

Referring now to FIG. 10, another embodiment of a stent 1000 haschannels of varying widths and depths on the exterior of the stent body.For example channel 1001 has a width that is greater than the width ofchannel 1003. The variable width and depth can be used to change theflow of fluids or friction to the lumen it is place in. Similar channelsmay also be formed on the interior side of a tubular stent. In theembodiment shown in FIG. 10, the stent 1000 has a tapered tip 1005 tofacilitate advancement of the stent inside a body lumen. The wide distalflare 1007 prevents migration and increases stability of the stent 900.The stent 1000 may have channels of shorter or longer pitches to enableincreases in fluid flow and stability. The stent 1000 may furtherinclude a center lumen for a guide wire or fluid flow.

Referring now to FIGS. 11A-11B another embodiment of a stent 1100 has alarger proximal end 1101 with a helical surface channel 1103. The stent1100 is in the shape of a cone or a cylinder with alternating variationin the diameter of the stent body. The surface channel 1103 may haveregions 1104, 1105 and 1106 with different shapes and depth in eachregion, so as to change the flow rate, flow volume, and/or in eachregion.

FIG. 12 shows another embodiment of a stent 1200. The pitch of the stentcan change in various zones of the stent. The stent has a smallerdiameter in the proximal end 1201 and larger diameter in the distal end1203. The stent 1200 may have an opening 1205 that is big enough toadapt a wire. The stent 1200 may have a gradual increasing or decreasingpitch. In another embodiment, the pitch may change in different sectionsof the stent to better contour to the anatomy.

Other embodiments of stents of the present application are shown inFIGS. 15-18.

FIG. 15 shows an embodiment of a stent 1500 with a conical tip 1501 toallow for ease of access into the area it will be placed, a flareddistal end 1503 for anchoring or prevention of migration into a lumen,out of a lumen, or within a lumen. The flares 1505 can be unidirectionalor bi directional.

FIG. 16 shows an embodiment of a stent 1600 with a conical end 1601 anda swollen middle section 1603. The stent 1600 may be made from anelastomer. In one embodiment, the elastomer may expands more in a areain the middle, the end, or in multiple locations of the stent body toincrease fluid flow by providing larger and deeper channels in thestent. In another embodiment, the end of the stent 1600 has ananti-migration mechanism that will expand to keep the stent in place.Anti-migration device at the distal end 1605 of the stent can be locatedanywhere along the length of the stent access.

FIG. 17 shows another embodiment of a stent 1700 with leaflets 1701 toform channels 1703. In this embodiment, the stent 1700 has a tapered end1705 to allow for ease of entry. The rotation of the sinusoidal channels1703 may be changed to adjust fluid flow, collapse ability, etc. Theleaflets attached to the cam 1707 can be folded over to allow thediameter of the stent 1700 to become smaller when being loaded into adeliver device or being place in a deliver tube like an endoscope. Thechannels walls can be straight, rounded, or a combination thereofdepending on the cavity or lumen where the stent is placed.

FIG. 18 shows another embodiment of a stent 1800. The stent 1800 is madein a way to allow the sinusoidal channel of the stent occur on theinside of the stent. The outside of the stent conforms to the anatomythe stent is placed in and flexibility is determined by the pitch of thesinusoidal channel. The inside of the stent forms the same sinusoidal asthe outside of the stent. In one embodiment, the stent 1800 is made insuch a way that it can be inserted in a screw in fashion.

A person or ordinary skill in the art would understand that otherfolding or interlocking may also be employed. The channel walls orleaflets can also be of varying thicknesses and lengths to provide thestent with desired rigidity, flexibility, pushability, trackability,luminal contact and/or absorption profile. For example, a stent madefrom bioabsorbable material may have leaflets that are thinner at thetip (where they touch the lumen wall) and thicker at the base (wherethey are attached to the cam), thus allowing for degradation from thetip to the base. In another embodiment, the cam itself can be cut invarious ways to change its diameter at different points to change thepushability and flexibility of the device.

FIG. 19A shows the basic design of another embodiment of a stent 1900.In one embodiment, the stent 1900 is made from a polymeric material. Incertain embodiments, the polymeric material may be Aquaprene 8020 withOpaciprene, Dioxaprene 100M with Opaciprene, or Lactoprene 7415 withOpaciprene. Appropriate grades of USD, PPD and MDP may also be selectedfor use in manufacturing the stent. In some embodiments, the stentcomprises a fast-absorbing polymer, such as USD5 (Aquaprene 8020: 20%PEG, 80% p-dioxanone). In other embodiments, the stent comprises amedium-absorbing polymer, such as PPD3 (Dioxaprene 100M:Poly(para-diaxanone). In still other embodiments, the stent comprises aslow-absorbing polymer, such as MDP3 (Lactoprene 7415: 74/15/11copolymer of lactide/trimethylene carbonate/caprolactone). In someembodiments, the lactide is the monomer L-lactide. In some embodiments,the stent is impregnated with a ˜1% to ˜40% BaSO₄ solution in a suitablecarrier. In further embodiments, the stent is impregnated with a ˜10% to˜30% BaSO₄ solution in a suitable carrier. In still further embodiments,the stent is impregnated with a ˜12% to ˜22% BaSO₄ solution in asuitable carrier. In particular embodiments, the stent is impregnatedwith a ˜17% BaSO₄ solution in a suitable carrier.

The stent length 1901 is variable, dependent upon the application orlocation the stent 1900 is to be used in. In some embodiments, the stentlength 1091 can be between about 5 mm and about 300 mm. In particularembodiments, the stent length 1091 is about 20, 40, 60, 80, 100, 150 or225 mm. In some embodiments, the stent 1900 has an outer diameter 1902of between about 1.8 mm and about 2.2 mm. In other embodiments, thestent 1900 has an outer diameter 1902 of between about 1.9 mm and about2.1 mm. In particular embodiments, the stent 1900 has an outer diameter1902 of about 2.0 mm. In some embodiments, the ends of the stent 1900are tapered to be narrower than the main body of the stent 1900. The“outer diameter” refers to the linear distance between the two farthestpoints on the device along a straight line that passes through thecenter of the device in a cross-section.

The stent 1900 of this embodiment is flexible. In some embodiments, thestent flexes after placement in the target location. In someembodiments, the body of the stent can tolerate a bend 1903 of betweenabout 90° and about 135° without experiencing a degradation of fluidflow rate. In other embodiments, the body of the stent can tolerate abend 1903 of between about 100° and about 125° without experiencing adegradation of fluid flow rate. In still other embodiments, the body ofthe stent can tolerate a bend 1903 of about 112° without experiencing adegradation of fluid flow rate.

In some embodiments, the body of the stent 1900 is curved, having acurvature 1913 with a radius of between about 10 mm and about 70 mm. Inother embodiments, the body of the stent 1900 has a curvature 1913 witha radius of between about 20 mm and about 60 mm. In still otherembodiments, the body of the stent 1900 has a curvature 1913 with aradius of between about 30 mm and about 50 mm. In particularembodiments, the body of the stent 1900 has a curvature 1913 with aradius of about 40 mm.

The stent 1900 comprises two anti-migration devices 1904 that expandoutwards from the elongated body of the stent 1900 so as to anchor thestent in position within a bodily lumen. In some embodiments, theanti-migration devices are elongated protrusions that extend from thestent and contact the tissue of the lumen in order to hold the stent inplace. It some embodiments, the tip of the anti-migration devices ispointed, so that the tip can embed in the tissue. In some embodiments,the anti-migration devices are held flush with the surface of the stentprior to and during deployment and are allowed to fold out followingplacement at the target site. The anti-migration devices 1904 are placedin proximity to the ends of the stent, however, one of ordinary skillwill understand that the placement of the anti-migration devices 1904 isnot limiting on the application. In some embodiments, the anti-migrationdevices 1904 are between about 1 mm and about 12 mm in length 1905. Infurther embodiments, the anti-migration devices 1904 are between about 3mm and about 10 mm in length 1905. In still further embodiments, theanti-migration devices 1904 are between about 5 mm and about 8 mm inlength 1905. In a particular embodiment, the anti-migration devices 1904are about 7 mm in length 1905. Furthermore, in some embodiments, theanti-migration devices 1904 are a distance 1906 of between about 1 mmand about 12 mm from each end of the stent 1900. In further embodiments,the anti-migration devices 1904 are a distance 1906 of between about 3mm and about 10 mm from each end of the stent 1900. In still furtherembodiments, the anti-migration devices 1904 are a distance 1906 ofbetween about 5 mm and about 8 mm from each end of the stent 1900. In aparticular embodiment, the anti-migration devices 1904 are a distance1906 of about 7 mm from each end of the stent 1900. In some embodiments,the anti-migration devices 1904 are the same distance 1906 from each endof the stent 1900. In other embodiments, the anti-migration devices 1904are different distances 1906 from each end of the stent 1900.

FIG. 19B is a 3-D rendering of the stent 1900. The end of thisperspective view shows that the stent has a single central lumen 1907.The longitudinal central lumen 1907 of the stent 1900 is formed withinthe polymeric material and provides a channel for a guide wire. Thenarrowing of the stent on either side of the central lumen 1907 createsopposing external channels 1908 for fluid flow on the external surfaceof the stent 1900. As shown in FIG. 19B, the stent 1900 is twisted,causing the opposing external channels 1908 to spiral around the stent1900.

FIG. 19C is a side view of the stent 1900, showing the spiraling of theexternal channels around the central lumen 1907 (dashed lines). Thepresent inventors have surprisingly found that the fluid flow throughthe external channels is optimized by controlling the number of twistsof the stent per inch (i.e., number of turns per 25.4 mm, shown in FIG.19C as 1909, wherein one twist is a 360 degree rotation around thecentral axis of the stent). In addition, the present inventors havefound that increasing the number of twists per inch (TPI)increases/improves the flexibility of the stent, as measured bydeflection of the stent material with an equivalent amount of forceapplied. Increasing the TPI (for example, from 1 TPI to 2 TPI or from 2TPI to 3 TPI) increases the amount of deflection, thereby indicatingthat higher TPI produces a more flexible stent. In some embodiments, thenumber of twists is at least, or more than, 1 twist per inch. In otherembodiments, the number of twists is at least, or more than, 1.5 twistsper inch. In still other embodiments, the number of twists is at least,or more than, 1.75 twists per inch. In yet other embodiments, the numberof twists is between about 1.5 and 2.5 twists per inch. In even otherembodiments, the number of twists is between about 1.75 and 2.25 twistsper inch. In still other embodiments, the number of twists is about 2twists per inch. In particular embodiments, the number of twists is atleast, or more than, 2 twists per inch. In further embodiments, thenumber of twists equals 2 twists per inch. In other further embodiments,the number of twists is more than 2 twists per inch. The twisting of thestent may be carried out by any means known to one of ordinary skill inthe art. In some embodiments, the stent may be formed in a straight,non-twisted, configuration, followed by twisting or machining to thedesired number of twists/inch. In other embodiments, the stent 1900 maybe formed or molded in the twisted shape. The polymer material fromwhich the stent 1900 is made may be fixed in place in the twistedposition by any means known to one of ordinary skill in the art, e.g., aheating process, etc.

FIG. 19D shows a cross-section view of the stent 1900 at line D-D ofFIG. 19C and looking towards one end of the stent 1900. In terms oforientation for describing the cross-section, the directions up, down,upper and lower refer direction lying on the main axis that bisects thecross-section of the stent into the longest mirror-image halves. Sidesand side-to-side refer to a cross axis that is perpendicular to the mainaxis. In some embodiments, the central channel 1907 is between about 0.8mm and about 1.2 mm in diameter. In other embodiments, the centralchannel 1907 is between about 0.9 mm and about 1.1 mm in diameter. Instill other embodiments, the central channel 1907 is between about 0.95mm and about 1.05 mm in diameter. In particular embodiments, the centralchannel 1907 is about 1 mm in diameter. In other particular embodiments,the central channel 1907 is 1 mm+/−0.1 mm in diameter. The “diameter” ofthe central channel refers to the linear distance between the twofarthest points within the lumen of the central channel along a straightline that passes through the center of the central channel in across-section.

Still referring to FIG. 19D, the cross-section of the stent comprises acentral circle 1919 that surrounds the central channel 1907 and upperand lower bolsters 1921 that overlap the central circle 1919 and, insome embodiments, each other. The sides of the central circle 1919,between the points where the bolsters 1921 intersect with the centralcircle 1919, form the minor, thinner, walls 1920 of the stent around thecentral channel 1907. In some embodiments, the thickness of the minorwalls 1920 is between about 0.1 mm and about 0.3 mm. In otherembodiments, the thickness of the minor walls 1920 is between about 0.15mm and about 0.25 mm. In particular embodiments, the thickness of theminor walls 1920 is about 0.2 mm+/−0.02 mm. In more particularembodiments, the thickness of the minor walls 1920 is about 0.2mm+/−0.01 mm.

Still referring to FIG. 19D, the upper and lower bolsters 1921 aregenerally elliptical, oval or circular in shape. In the case of an ovalor elliptical bolster 1921, the longest longitudinal axis of the bolster1921 may lie oriented perpendicular to the main axis of the crosssection of the stent, as shown in FIG. 19D. In some embodiments, thelongest longitudinal axis of an oval or elliptical bolster 1921 may lieoriented along the main axis of the cross section of the stent. Thebolsters 1921 form the major, thicker, walls of the stent.

In some embodiments, the thickness of the major walls 1922 is betweenabout 0.3 mm and about 0.7 mm at the main axis. In other embodiments,the thickness of the major walls 1922 is between about 0.4 mm and about0.6 mm at the main axis. In particular embodiments, the thickness of themajor walls 1922 is about 0.5 mm+/−0.05 mm at the main axis. In moreparticular embodiments, the thickness of the major walls 1922 is about0.5 mm+/−0.025 mm at the main axis.

In some embodiments, the bolsters 1921 have a side-to-side thickness ofbetween about 1.4 mm and about 1.8 mm. In other embodiments, thebolsters 1921 have a side-to-side thickness of between about 1.5 mm andabout 1.78 mm. In particular embodiments, the bolsters 1921 have aside-to-side thickness of about 1.61 mm+/−0.16 mm. In more particularembodiments, the bolsters 1921 have a side-to-side thickness of about1.61 mm+/−0.08 mm.

FIG. 19E shows a cross-sectional view of an alternative embodiment ofthe stent 1900 at line D-D of FIG. 19C and looking towards one end ofthe stent 1900 where the bolsters 1921 are of a circular shape. Thesides of the central circle 1919, between the points where the bolsters1921 intersect with the central circle 1919, form the minor, thinner,walls 1920 of the stent around the central channel 1907. In someembodiments, the thickness of the minor walls 1920 is between about 0.1mm and about 0.3 mm. In other embodiments, the thickness of the minorwalls 1920 is between about 0.15 mm and about 0.25 mm. In particularembodiments, the thickness of the minor walls 1920 is about 0.2mm+/−0.02 mm. In more particular embodiments, the thickness of the minorwalls 1920 is about 0.2 mm+/−0.01 mm. In some embodiments, the diameterof the circular bolsters 1921 is the same as the diameter of the centralcircle 1919. In other embodiments, the diameter of the circular bolsters1921 is greater than the diameter of the central circle 1919. In someembodiments, the thickness of the major walls 1922 is between about 0.3mm and about 0.7 mm at the main axis. In other embodiments, thethickness of the major walls 1922 is between about 0.4 mm and about 0.6mm at the main axis. In particular embodiments, the thickness of themajor walls 1922 is about 0.5 mm+/−0.05 mm at the main axis. In moreparticular embodiments, the thickness of the major walls 1922 is about0.5 mm+/−0.025 mm at the main axis.

FIG. 20A shows the basic design of another embodiment of a stent 2000.In one embodiment, the stent 2000 is made from a polymeric material. Incertain embodiments, the polymeric material may be Aquaprene 8020 withOpaciprene, Dioxaprene 100M with Opaciprene or Lactoprene 7415 withOpaciprene. Appropriate grades of USD, PPD and MDP may also be selectedfor use in manufacturing the stent. In some embodiments, the stentcomprises a fast-absorbing polymer, such as USD5 (Aquaprene 8020: 20%PEG, 80% p-dioxanone). In other embodiments, the stent comprises amedium-absorbing polymer, such as PPD3 (Dioxaprene 100M:Poly(para-diaxanone). In still other embodiments, the stent comprises aslow-absorbing polymer, such as MDP3 (Lactoprene 7415: 74/15/11copolymer of lactide/trimethylene carbonate/caprolactone). In someembodiments, the stent is impregnated with a ˜1% to ˜40% BaSO₄ solutionin a suitable carrier. In further embodiments, the stent is impregnatedwith a ˜10% to ˜30% BaSO₄ solution in a suitable carrier. In stillfurther embodiments, the stent is impregnated with a ˜12% to ˜22% BaSO₄solution in a suitable carrier. In particular embodiments, the stent isimpregnated with a ˜17% BaSO₄ solution in a suitable carrier.

The stent length 2001 is variable, dependent upon the application orlocation the stent 2000 is to be used in. In some embodiments, the stentlength 2001 can be between about 20 mm and about 300 mm. In particularembodiments, the stent length 2001 is about 40, 60, 80, 100, 120, 150,225 or 250 mm. In some embodiments, the stent 2000 has an outer diameter2002 of between about 2.0 mm and about 3.2 mm. In other embodiments, thestent 2000 has an outer diameter 2002 of between about 2.34 mm and about2.86 mm. In still other embodiments, the stent 2000 has an outerdiameter 2002 of between about 2.5 mm and about 2.7 mm. In particularembodiments, the stent 2000 has an outer diameter 2002 of about 2.6mm+/−0.26 mm. In more particular embodiments, the stent 2000 has anouter diameter 2002 of about 2.6 mm+/−0.13 mm. In some embodiments, theends of the stent 2000 are tapered to be narrower than the main body ofthe stent 2000. The “outer diameter” refers to the linear distancebetween the two farthest points on the device along a straight line thatpasses through the center of the device in a cross-section.

The stent 2000 of this embodiment is flexible. In some embodiments, thestent flexes after placement in the target location. In someembodiments, the body of the stent can tolerate a bend 2003 of betweenabout 90° and about 135° without experiencing a degradation of fluidflow rate. In other embodiments, the body of the stent can tolerate abend 2003 of between about 100° and about 125° without experiencing adegradation of fluid flow rate. In still other embodiments, the body ofthe stent can tolerate a bend 2003 of about 112° without experiencing adegradation of fluid flow rate.

In some embodiments, the body of the stent 2000 is curved, having acurvature 2013 with a radius of between about 10 mm and about 70 mm. Inother embodiments, the body of the stent 2000 has a curvature 2013 witha radius of between about 20 mm and about 60 mm. In still otherembodiments, the body of the stent 2000 has a curvature 2013 with aradius of between about 30 mm and about 50 mm. In particularembodiments, the body of the stent 2000 has a curvature 2013 with aradius of about 40 mm.

The stent 2000 comprises two anti-migration devices 2004 that expandoutwards from the elongated body of the stent 2000 so as to anchor thestent in position within a bodily lumen. In some embodiments, theanti-migration devices are elongated protrusions that extend from thestent and contact the tissue of the lumen in order to hold the stent inplace. It some embodiments, the tip of the anti-migration devices ispointed, so that the tip can embed in the tissue. In some embodiments,the anti-migration devices are held flush with the surface of the stentprior to and during deployment and are allowed to fold out followingplacement at the target site. The anti-migration devices 2004 are placedin proximity to the ends of the stent, however, one of ordinary skillwill understand that the placement of the anti-migration devices 2004 isnot limiting on the application. In some embodiments, the anti-migrationdevices 2004 are between about 1 mm and about 12 mm in length 2005. Infurther embodiments, the anti-migration devices 2004 are between about 3mm and about 10 mm in length 2005. In still further embodiments, theanti-migration devices 2004 are between about 5 mm and about 8 mm inlength 2005. In a particular embodiment, the anti-migration devices 2004are about 7 mm in length 2005. Furthermore, in some embodiments, theanti-migration devices 2004 are a distance 2006 of between about 1 mmand about 12 mm from each end of the stent 2000. In further embodiments,the anti-migration devices 2004 are a distance 2006 of between about 3mm and about 10 mm from each end of the stent 2000. In still furtherembodiments, the anti-migration devices 2004 are a distance 2006 ofbetween about 5 mm and about 8 mm from each end of the stent 2000. In aparticular embodiment, the anti-migration devices 2004 are a distance2006 of about 7 mm from each end of the stent 2000. In some embodiments,the anti-migration devices 2004 are the same distance 2006 from each endof the stent 2000. In other embodiments, the anti-migration devices 2004are different distances 2006 from each end of the stent 2000.

FIG. 20B is a 3-D rendering of the stent 2000. The end of thisperspective view shows that the stent has a single central lumen 2007.The longitudinal central lumen 2007 of the stent 2000 is formed withinthe polymeric material and provides a channel for a guide wire. Thenarrowing of the stent on either side of the central lumen 2007 createsopposing external channels 2008 for fluid flow on the external surfaceof the stent 2000. As shown in FIG. 20B, the stent 2000 is twisted,causing the opposing external channels 2008 to spiral around the stent2000. FIG. 20C is a side view of the stent 2000, showing the spiralingof the external channels around the central lumen 2007 (dashed lines).The inventors have surprisingly found that the fluid flow through theexternal channels is optimized by controlling the number of twists ofthe stent per inch (i.e., number of turns per 25.4 mm, shown in FIG. 20Cas 2009, wherein one twist is a 360 degree rotation around the centralaxis of the stent). In addition, the present inventors have found thatincreasing the number of twists per inch (TPI) increases/improves theflexibility of the stent, as measured by deflection of the stentmaterial with an equivalent amount of force applied. Increasing the TPI(for example, from 1 TPI to 2 TPI or from 2 TPI to 3 TPI) increases theamount of deflection, thereby indicating that higher TPI produces a moreflexible stent. In some embodiments, the number of twists is at least,or more than, 1 twist per inch. In other embodiments, the number oftwists is at least, or more than, 1.5 twists per inch. In still otherembodiments, the number of twists is at least, or more than, 1.75 twistsper inch. In yet other embodiments, the number of twists is betweenabout 1.5 and 2.5 twists per inch. In even other embodiments, the numberof twists is between about 1.75 and 2.25 twists per inch. In still otherembodiments, the number of twists is about 2 twists per inch. Inparticular embodiments, the number of twists is at least, or more than,2 twists per inch. In further embodiments, the number of twists equals 2twists per inch. In other further embodiments, the number of twists ismore than 2 twists per inch. The twisting of the stent may be carriedout by any means known to one of ordinary skill in the art. In someembodiments, the stent may be formed in a straight, non-twisted,configuration, followed by twisting or machining to the desired numberof twists/inch. In other embodiments, the stent 2000 may be formed ormolded in the twisted shape. The polymer material from which the stent2000 is made may be fixed in place in the twisted position by any meansknown to one of ordinary skill in the art, e.g., a heating process, etc.

FIG. 20D shows a cross-section view of the stent 2000 at line C-C ofFIG. 20C and looking towards one end of the stent 2000. In someembodiments, the central channel 2007 is between about 0.8 mm and about1.2 mm in diameter. In other embodiments, the central channel 2007 isbetween about 0.9 mm and about 1.1 mm in diameter. In still otherembodiments, the central channel 2007 is between about 0.95 mm and about1.05 mm in diameter. In particular embodiments, the central channel 2007is about 1 mm+/−0.1 mm in diameter. The “diameter” of the centralchannel refers to the linear distance between the two farthest pointswithin the lumen of the central channel along a straight line thatpasses through the center of the central channel in a cross-section.

Still referring to FIG. 20D, the cross-section of the stent comprises acentral circle 2019 that surrounds the central channel 2007 and upperand lower bolsters 2021 that overlap the central circle 2019 and, insome embodiments, each other. The sides of the central circle 2019,between the points where the bolsters 2021 intersect with the centralcircle 2019, form the minor, thinner, walls 2020 of the stent around thecentral channel 2007. In some embodiments, the thickness of the minorwalls 2020 is between about 0.1 mm and about 0.3 mm. In otherembodiments, the thickness of the minor walls 2020 is between about 0.15mm and about 0.25 mm. In particular embodiments, the thickness of theminor walls 2020 is about 0.2 mm+/−0.02 mm. In more particularembodiments, the thickness of the minor walls 2020 is about 0.2mm+/−0.01 mm.

Still referring to FIG. 20D, the upper and lower bolsters 2021 aregenerally elliptical, oval or circular in shape. In the case of an ovalor elliptical bolster 2021, the longest longitudinal axis of the bolster2021 may lie oriented along the main axis of the cross section of thestent, as shown in FIG. 20D. In some embodiments, the longestlongitudinal axis of an oval or elliptical bolster 2021 may lie orientedperpendicular to the main axis of the cross section of the stent. Thebolsters 2021 form the major, thicker, walls of the stent.

In some embodiments, the thickness of the major walls 2022 is betweenabout 0.6 mm and about 1.0 mm at the main axis. In other embodiments,the thickness of the major walls 2022 is between about 0.7 mm and about0.9 mm at the main axis. In particular embodiments, the thickness of themajor walls 2022 is about 0.8 mm+/−0.08 mm at the main axis. In moreparticular embodiments, the thickness of the major walls 2022 is about0.8 mm+/−0.04 mm at the main axis.

In some embodiments, the bolsters 2021 have a side-to-side thickness ofabout 1.4 mm+/−0.14 mm. In more particular embodiments, the bolsters2021 have a side-to-side thickness of about 1.4 mm+/−0.07 mm.

FIG. 21A shows the basic design of another embodiment of a stent 2100.In one embodiment, the stent 2100 is made from a polymeric material. Incertain embodiments, the polymeric material may be Aquaprene 8020 withOpaciprene, Dioxaprene 100M with Opaciprene, or Lactoprene 7415 withOpaciprene. Appropriate grades of USD, PPD and MDP may also be selectedfor use in manufacturing the stent. In some embodiments, the stentcomprises a fast-absorbing polymer, such as USD5 (Aquaprene 8020: 20%PEG, 80% p-dioxanone). In other embodiments, the stent comprises aslow-absorbing polymer, such as PPD3 (Dioxaprene 100M:Poly(para-diaxanone). In still other embodiments, the stent comprises aslow-absorbing polymer, such as MDP3 (Lactoprene 7415: 74/15/11copolymer of lactide/trimethylene carbonate/caprolactone). In someembodiments, the stent is impregnated with a ˜1% to ˜40% BaSO₄ solutionin a suitable carrier. In further embodiments, the stent is impregnatedwith a ˜10% to ˜30% BaSO₄ solution in a suitable carrier. In stillfurther embodiments, the stent is impregnated with a ˜12% to ˜22% BaSO₄solution in a suitable carrier. In particular embodiments, the stent isimpregnated with a ˜17% BaSO₄ solution in a suitable carrier.

The stent length 2101 is variable, dependent upon the application orlocation the stent 2100 is to be used in. In some embodiments, the stentlength 2101 can be between about 20 mm and about 300 mm. In particularembodiments, the stent length 2101 is about 40, 60, 80, 100, 120, 150,200 or 225 mm. In some embodiments, the stent 2100 has an outer diameter2102 of between about 2.5 mm and about 5 mm. In other embodiments, thestent 2100 has an outer diameter 2102 of between about 3.06 mm and about3.74 mm. In still other embodiments, the stent 2100 has an outerdiameter 2102 of between about 3.3 mm and about 3.5 mm. In particularembodiments, the stent 2100 has an outer diameter 2102 of about3.4+/−0.34 mm. In more particular embodiments, the stent 2100 has anouter diameter 2102 of about 3.4+/−0.17 mm. In some embodiments, theends of the stent 2100 are tapered to be narrower than the main body ofthe stent 2100. The “outer diameter” refers to the linear distancebetween the two farthest points on the device along a straight line thatpasses through the center of the device in a cross-section.

The stent 2100 of this embodiment is flexible. Upon final placement ofthe stent 2100, in some embodiments, the body of the stent can toleratea bend 2103 of between about 90° and about 135° without experiencing adegradation of fluid flow rate. In other embodiments, the body of thestent can tolerate a bend 2103 of between about 100° and about 125°without experiencing a degradation of fluid flow rate. In still otherembodiments, the body of the stent can tolerate a bend 2103 of about112° without experiencing a degradation of fluid flow rate.

In some embodiments, the body of the stent 2100 is curved, having acurvature 2113 with a radius of between about 10 mm and about 70 mm. Inother embodiments, the body of the stent 2100 has a curvature 2013 witha radius of between about 20 mm and about 60 mm. In still otherembodiments, the body of the stent 2100 has a curvature 2113 with aradius of between about 30 mm and about 50 mm. In particularembodiments, the body of the stent 2100 has a curvature 2113 with aradius of about 40 mm.

The stent 2100 comprises two anti-migration devices 2104 that expandoutwards from the elongated body of the stent 2100 so as to anchor thestent in position within a bodily lumen. The anti-migration devices 2104are placed in proximity to the ends of the stent, however, one ofordinary skill will understand that the placement of the anti-migrationdevices 2104 is not limiting on the application. In some embodiments,the anti-migration devices 2104 are between about 1 mm and about 12 mmin length 2105. In further embodiments, the anti-migration devices 2104are between about 3 mm and about 10 mm in length 2105. In still furtherembodiments, the anti-migration devices 2104 are between about 5 mm andabout 8 mm in length 2105. In a particular embodiment, theanti-migration devices 2104 are about 7 mm in length 2105. Furthermore,in some embodiments, the anti-migration devices 2104 are a distance 2106of between about 1 mm and about 12 mm from each end of the stent 2100.In further embodiments, the anti-migration devices 2104 are a distance2106 of between about 3 mm and about 10 mm from each end of the stent2100. In still further embodiments, the anti-migration devices 2104 area distance 2106 of between about 5 mm and about 8 mm from each end ofthe stent 2100. In a particular embodiment, the anti-migration devices2104 are a distance 2106 of about 7 mm from each end of the stent 2100.In some embodiments, the anti-migration devices 2104 are the samedistance 2106 from each end of the stent 2100. In other embodiments, theanti-migration devices 2104 are different distances 2106 from each endof the stent 2100.

FIG. 21B is a 3-D rendering of the stent 2100. The end of thisperspective view shows that the stent has a single central lumen 2107.The longitudinal central lumen 2107 of the stent 2100 is formed withinthe polymeric material and provides a channel for a guide wire. As shownin FIG. 21B, the stent 2100 is twisted, causing the opposing externalchannels 2108, created by the narrower side-to-side axis of the stent,to spiral around the stent 2100.

FIG. 21C is a side view of the stent 2100, showing the spiraling of theexternal channels 2108 around the central lumen 2107 (dashed lines). Theinventors have surprisingly found that the fluid flow through theexternal channels 2108 is optimized by controlling the number of twistsof the stent per inch (i.e., number of turns per 25.4 mm, shown in FIG.21C as 2109, wherein one twist is a 360 degree rotation around thecentral axis of the stent). In addition, the present inventors havefound that increasing the number of twists per inch (TPI)increases/improves the flexibility of the stent, as measured bydeflection of the stent material with an equivalent amount of forceapplied. Increasing the TPI (for example, from 1 TPI to 2 TPI or from 2TPI to 3 TPI) increases the amount of deflection, thereby indicatingthat higher TPI produces a more flexible stent. In some embodiments, thenumber of twists is at least, or more than, 1 twist per inch. In otherembodiments, the number of twists is at least, or more than, 1.5 twistsper inch. In still other embodiments, the number of twists is at least,or more than, 1.75 twists per inch. In yet other embodiments, the numberof twists is between about 1.5 and 2.5 twists per inch. In even otherembodiments, the number of twists is between about 1.75 and 2.25 twistsper inch. In still other embodiments, the number of twists is about 2twists per inch. In particular embodiments, the number of twists is atleast, or more than, 2 twists per inch. In further embodiments, thenumber of twists equals 2 twists per inch. In other further embodiments,the number of twists is more than 2 twists per inch. The twisting of thestent may be carried out by any means known to one of ordinary skill inthe art. In some embodiments, the stent may be formed in a straight,non-twisted, configuration, followed by twisting or machining to thedesired number of twists/inch. In other embodiments, the stent 2100 maybe formed or molded in the twisted shape. The polymer material fromwhich the stent 2100 is made may be fixed in place in the twistedposition by any means known to one of ordinary skill in the art, e.g., aheating process, etc.

FIG. 21D shows a cross-section view of the stent 2100 at line A-A ofFIG. 21C. In terms of orientation for describing the cross-section, thedirections up, down, upper and lower refer direction lying on the mainaxis that bisects the cross-section of the stent into the longestmirror-image halves. Sides and side-to-side refer to a cross axis thatis perpendicular to the main axis. In some embodiments, the centralchannel 2107 is between about 0.8 mm and about 1.2 mm in diameter. Inother embodiments, the central channel 2107 is between about 0.9 mm andabout 1.1 mm in diameter. In still other embodiments, the centralchannel 2107 is between about 0.95 mm and about 1.05 mm in diameter. Inparticular embodiments, the central channel 2107 is about 1 mm indiameter. In other particular embodiments, the central channel 2107 is 1mm+/−0.1 mm in diameter. In some embodiments, the central channel iscircular in cross section, in other embodiments, the central channel isoval or elliptical in cross section. The “diameter” of the centralchannel refers to the linear distance between the two farthest pointswithin the lumen of the central channel along a straight line thatpasses through the center of the central channel in a cross-section.

Still referring to FIG. 21D, the cross-section of the stent comprises acentral circle 2119 that surrounds the central channel 2107 and upperand lower bolsters 2121 that overlap the central circle 2119 and, insome embodiments, each other. The sides of the central circle 2119,between the points where the bolsters 2121 intersect with the centralcircle 2119, form the minor, thinner, walls 2120 of the stent around thecentral channel 2107. In some embodiments, the thickness of the minorwalls 2120 is between about 0.1 mm and about 0.3 mm. In otherembodiments, the thickness of the minor walls 2120 is between about 0.15mm and about 0.25 mm. In particular embodiments, the thickness of theminor walls 2120 is about 0.2 mm+/−0.02 mm. In more particularembodiments, the thickness of the minor walls 2120 is about 0.2mm+/−0.01 mm.

Still referring to FIG. 21D, the upper and lower bolsters 2121 aregenerally elliptical, oval or circular in shape. In the case of an ovalor elliptical bolster 2121, the longest longitudinal axis of the bolster2121 may lie oriented along the main axis of the cross section of thestent, as shown in FIG. 21D. In some embodiments, the longestlongitudinal axis of an oval or elliptical bolster 2121 may lie orientedperpendicular to the main axis of the cross section of the stent. Thebolsters 2121 form the major, thicker, walls of the stent.

In some embodiments, the thickness of the major walls 2122 is betweenabout 0.9 mm and about 1.5 mm at the main axis. In other embodiments,the thickness of the major walls 2122 is between about 1.0 mm and about1.4 mm at the main axis. In still other embodiments, the thickness ofthe major walls 2122 is between about 1.1 mm and about 1.3 mm at themain axis. In particular embodiments, the thickness of the major walls2122 is about 1.2 mm+/−0.12 mm at the main axis. In more particularembodiments, the thickness of the major walls 2122 is about 1.2mm+/−0.06 mm at the main axis.

In some embodiments, the bolsters 2121 have a side-to-side thickness ofabout 1.4 mm+/−0.14 mm. In more particular embodiments, the bolsters2121 have a side-to-side thickness of about 1.4 mm+/−0.07 mm.

FIG. 21E shows an alternative cross-section for an embodiment of thestent 2100 and FIG. 21F shows the corresponding 3-D view. In someembodiments, the bolsters 2121 have a side-to-side thickness of betweenabout 1.5 mm and about 1.9 mm. In other embodiments, the bolsters 1921have a side-to-side thickness of between about 1.6 mm and about 1.8 mm.In particular embodiments, the bolsters 1921 have a side-to-sidethickness of about 1.7 mm+/−0.17 mm. In more particular embodiments, thebolsters 1921 have a side-to-side thickness of about 1.7 mm+/−0.085 mm.

FIG. 21G shows another alternative cross-section for an embodiment ofthe stent 2100 and FIG. 21H shows the corresponding 3-D view. In someembodiments, the bolsters 2121 have a side-to-side thickness of betweenabout 1.4 mm and about 1.5 mm. In particular embodiments, the bolsters2121 have a side-to-side thickness of about 1.45 mm+/−0.145 mm. In moreparticular embodiments, the bolsters 2121 have a side-to-side thicknessof about 1.45 mm+/−0.07 mm. FIG. 22A shows an exemplary alternativefeature for the stents described in FIGS. 19A through 21H, wherein thejunctions between the central circle and the bolsters are tapered orrounded. FIG. 22B is a 3-D rendering of the exemplary stent of FIG. 22A.

A biodegradable stent of the present application is useful for thetreatment or palliation of strictures of a lumen in a subject in needthereof. In some embodiments, the lumen is a duct. In some furtherembodiments, the duct is a bile duct. In some still further embodiments,the bile duct is a hepatic, cystic, common bile or pancreatic duct. Insome embodiments, the stricture is caused by, co-occurring with orrelated to a malignancy or a benign disease or condition of the liver,pancreas, duodenum, gall bladder or biliary tree. A biodegradable stentof the present application provides less complications in a subject,does not require costly removal procedures, has a lower clinical costbecause it does not need sequential replacement and reduces loss of worktime for the subject in need thereof.

In some embodiments, a biodegradable stent of the present applicationdegrades by hydrolysis. In some embodiments, degradation of thebiodegradable stent occurs on the outer surfaces, wherein the outerlayer is degraded off and the stent progressively degrades from theoutside towards the center.

A stent of the present application is capable of opening the lumen of aduct and allows bile to drain away. The present stent is biocompatibleaccording to ISO 10993. The present stent is capable of withstandingcompression without obstructing a duct. The present stent is loadableinto a duodenal scope. The flexibility and column strength of thepresent stent is high enough to push the stent from the scope into aduct and can be deployed in a target location, and is visible, underfluoroscopy. A stent of the present application is insertable into aduct without perforating or otherwise damaging the duct. The ends of thestent minimize tissue granulation and the stent has high friction toprevent migration of the stent from the target location, while beingcapable of repositioning after deployment. The present stent isremovable after implantation without damage to the tissue of the lumen.A stent of the present invention has a shelf life of 1 to 2 years aftersterilization.

The present stent is typically made from a polymer material, plastics,metals, or alloys. Notable variations exist within each type. In certainembodiments, the stent is made from a non-polymer material. Examples ofsuch materials include, but are not limited to, stainless steel, cobaltalloys such as cobalt-chromium, titanium alloys, tantalum, niobium,tungsten, molybdenum and nitinol. For example, self-expanding metalstents are generally made from nitinol, while some balloon-expandablemetal stents are made from stainless steel. A coating, such aspolyurethane coating, may be used to prevent non-polymer stent materialfrom coming into direct contact with its surroundings. The coating slowsdown the rate of in-growth, allowing the stent to remain in the patientwith a lower potential for side effects.

The stent may also be made with a bioabsorbable material. Examples ofbioabsorbable materials include, but are not limited to, polylactic acidor polylactide (PLA), polyglycolic acid or polyglycolide (PGA),poly-ε-caprolactone (PCL), polyhydroxybutyrate (PHB), polyethyleneglycol (PEG), p-dioxanone, poly-(p-dioxanone) (PPDO), trimethylenecarbonate, caprolactate and co-polymers thereof.

In one embodiment, the bioabsorbable material is degraded based onvarying levels of pH. For example, the material may be stable at aneutral pH but degrades at a high pH. Examples of such materialsinclude, but are not limited to chitin and chitosan. In anotherembodiment, the bioabsorbable material is degradable by enzymes, such aslysozymes.

In another embodiment, the polymers include transparent plasticpolymers, thermoplastic polyurethane or silicone polymers.

In another embodiment, the elongated body comprises a combination of apolymer and a non-polymer material.

In another related embodiment, the elongated stent body is made of amagnesium and chitin alloy.

In another related embodiment, the elongated stent body is made with amagnesium core coated with a chitin chitosan, N-acylchitosan hydrogelouter layer. The magnesium core may additionally include rare earthmaterials.

In another related embodiment, the elongated stent body is made of achitin and chitosan, N-acylchitosan hydrogel and magnesium alloy withraw earth elements.

In another embodiment, the bioabsorbable material may absorb moistureand expand in situ at the treatment site. For example, the stent made ofchitin or a variable copolymer of chitin and PLGA or chitin andmagnesium and other rare earth minerals would swell once it comes intocontact with various body fluids. In one embodiment, the stent has apre-implantation diameter D_(pre) (i.e., dry diameter) of 2.8 mm and isexpandable to a post-implantation diameter D_(post), (i.e., wetdiameter) of 3.3 mm after exposure to body liquid in a lumen. As usedhereinafter, the “pre-implantation diameter D_(pre)” refers to thelargest diameter of a stent body before implantation and the“post-implantation diameter D_(post)” refers to the largest diameter ofthe stent body after implantation.

In some embodiments, the stent is made of a fast-absorbing bioabsorbablematerial that degrades within about two to four weeks. In particularembodiments, the fast-absorbing bioabsorbable material is a mixture orcombination of PEG and p-dioxanone. In a further embodiment, PEGcomprises about 10-30% and p-dioxanone comprises about 70-90% of themixture or combination. In a still further embodiment, PEG comprisesabout 15-25% and p-dioxone comprises about 75-85% of the mixture orcombination. In an even further embodiment, PEG comprises about 12-22%and p-dioxanone comprises about 78-82% of the mixture or combination. Ina yet further embodiment, PEG comprises about 20% and p-dioxanonecomprises about 80% of the mixture or combination.

In some embodiments, the stent is made of a medium-absorbingbioabsorbable material that degrades within about three to six weeks. Inparticular embodiments, the medium-absorbing bioabsorbable material isPPDO, or a copolymer thereof.

In some embodiments, the stent is made of a medium-to-slow-absorbingbioabsorbable material that degrades within about six week to fourmonths.

In some embodiments, the stent is made of a slow-absorbing bioabsorbablematerial that degrades within about four to six months. In particularembodiments, the fast-absorbing bioabsorbable material is a copolymer oflactide, trimethylene carbonate and caprolactate. In particularembodiments, the copolymer comprises a percentage composition ofPLA/trimethylene carbonate/caprolactate that is about 70-80/10-20/5-15,respectively. In further embodiments, the copolymer comprises apercentage composition of PLA/trimethylene carbonate/caprolactate thatis about 72-76/13-17/9-13, respectively. In still further embodiments,the copolymer comprises a percentage composition of PLA/trimethylenecarbonate/caprolactate that is about 74/15/11, respectively.

In some embodiments, the bioabsorbable material is coated or impregnatedwith a biocompatible radio-opaque substance to aid in visualization ofthe stent during or after emplacement, for example by fluoroscopy orx-ray. In some embodiments, the radio-opaque substance is a BaSO₄solution. In further embodiments, the solution comprises about 10-25%BaSO₄. In still further embodiments, the solution comprises about 12-22%BaSO₄. In even further embodiments, the solution comprises about 17%BaSO₄. In some embodiments, the radio-opaque substance comprises metalparticles. In further embodiments, the particles are nanoparticles. Inexemplary non-limiting embodiments, the metal comprises tantalum.

In another embodiment, the bioabsorbable material is embedded with, orconfigured to carry, various agents or cells. The agents may be coupledto the outer and/or inner surfaces of stent body or integrated into thebioabsorbable material itself. In one embodiment, the bioabsorbablestent has a hollow center lumen so that agents may be placed inside thelumen to increase the dose release. The stent can additionally havemultiple reservoirs, one inside the other, so that when the outer layeris absorbed the next reservoir is exposed and a further release of alarger dose of the chosen agents or cells. The chosen agent or cells mayalso be mixed with the polymer for sustained release.

Examples of agents that can be embedded into or carried by a stentinclude, but are not limited to, small molecule drugs, biologicals andgene transfer vectors. Examples of small molecule drugs include, but arenot limited to, sirolumus, rapamycian, and other antiproliferatingagent.

Examples of biologicals include, but are not limited to, antimicrobialagents and chemotherapeutic agents.

The term “antimicrobial agent” as used in the present application meansantibiotics, antiseptics, disinfectants and other synthetic moieties,and combinations thereof, that are soluble in organic solvents such asalcohols, ketones, ethers, aldehydes, acetonitrile, acetic acid, formicacid, methylene chloride and chloroform. Classes of antibiotics that canpossibly be used include tetracyclines (i.e., minocycline), rifamycins(i.e., rifampin), macrolides (i.e., erythromycin), penicillins (i.e.,nafcillin), cephalosporins (i.e., cefazolin), other beta-lactamantibiotics (imipenem, aztreonam), aminoglycosides (i.e., gentamicin),chloramphenicol, sulfonamides (i.e., sulfamethoxazole), glycopeptides(i.e., vancomycin), quinolones (i.e., ciprofloxacin), fusidic acid,trimethoprim, metronidazole, clindamycin, mupirocin, polyenes (i.e.,amphotericin B), azoles (i.e., fluconazole) and beta-lactam inhibitors(i.e., sulbactarn).

Examples of specific antibiotics that can be used include minocycline,rifainpin, erythromycin, nafcillin, cefazolin, imipenem, aztreonam,gentamicin, sulfamethoxazole, vancomycin, ciprofloxacin, trimethoprim,metronidazole, clindamycin, teicoplanin, mupirocin, azithromycin,clarithromycin, ofloxacin, lomefloxacin, norfiloxacin, nalidixic acid,sparfloxacin, pefloxacin, amifloxacin, enoxacin, fleroxacin,temafloxacin, tosufloxacin, clinafloxacin, sulbactam, clavulanic acid,amphotericin B, fluconazole, itraconazole, ketoconazole and nystatin.Other examples of antibiotics, such as those listed in U.S. Pat. No.4,642,104, herein incorporated by reference, will readily suggestthemselves to those of ordinary skill in the art. Examples ofantiseptics and disinfectants are thymol, a-terpineol,methylisothiazolone, cetylpyridinium, chloroxylenol, hexachlorophene,cationic biguanides (i.e., chlorhexidine, cyclohexidine),methylenechloride, iodine and iodophores (i.e., povidone-iodine),triclosan, firanmedical preparations (i.e., nitrofurantoin,nitrolurazone), methenamine, aldehydes (i.e., glutaraldehyde,formaldehyde) and alcohols. Other examples of antiseptics anddisinfectants will readily suggest themselves to those of ordinary skillin the art.

The stent of the present application may also be prepared withantimicrobial agents in other ways customary in the art. For example,the stent may be made in its entirety or in part of an antimicrobialpolymer, or at least one surface of the stent may have embedded, by ionbeam assisted deposition or co-extrusion techniques, therein with atomsof an antimicrobial polymer. Other suitable examples can be found in theart, for example, U.S. Pat. No. 5,520,664, which is incorporated hereinby reference.

Chemotherapeutic agents can be coupled with the stent of the presentapplication in a manner analogous to that of antimicrobial agents.Exemplary chemotherapeutic agents include but are not limited tocis-platinum, paclitaxol, 5-flourouracial, gemcytobine and navelbine.The chemotherapeutic agents are generally grouped as DNA-interactiveagents, antimetabolites, tubulin-interactive agents, hormonal agents,hormone-related agents, and others such as asparaginase or hydroxyurea.Each of the groups of chemotherapeutic agents can be further divided bytype of activity or compound. The chemotherapeutic agents used incombination with the anti-cancer agents or benzimidazoles of thisapplication include members of all of these groups. For a detaileddiscussion of the chemotherapeutic agents and their method ofadministration, see Dorr, et al, Cancer Chemotherapy Handbook, 2dedition, pages 15-34, Appleton & Lange (Connecticut, 1994), hereinincorporated by reference.

Examples of DNA-Interactive agents include, but are not limited to,alkylating agents, DNA strand-breakage agents; intercalating andnonintercalating topoisomerase II inhibitors, and DNA minor groovebinders. Alkylating agents generally react with a nucleophilic atom in acellular constituent, such as an amino, carboxyl, phosphate, orsulfhydryl group in nucleic acids, proteins, amino acids, orglutathione. Examples of alkylating agents include, but are not limitedto, nitrogen mustards, such as chlorambucil, cyclophosphamide,isofamide, mechlorethainine, Melphalan, uracil mustard; aziridines, suchas thiotepa; methanesulfonate esters such as busulfan; nitroso, ureas,such as cannustine, lomustine, streptozocin; platinum complexes, such ascisplatin, carboplatin; bioreductive alkylator, such as mitomycin, andprocarbazine, dacarbazine and altretamine. DNA strand breaking agentsinclude, but are not limited to, bleomycin. Intercalating DNAtopoisomerase II inhibitors include, but are not limited to,intercalators such as amsacrine, dactinomycin, daunorubicin,doxorubicin, idarubicin, and mitoxantrone.

Nonintercalating DNA topoisomerase II inhibitors include, but are notlimited to etoposide and teniposide. DNA minor groove binders include,but are not limited to, plicamycin.

Antimetabolites interfere with the production of nucleic acids by one orthe other of two major mechanisms. Some of the drugs inhibit productionof the deoxyribonucleoside triphosphates that are immediate precursorsfor DNA synthesis, thus inhibiting DNA replication. Some of thecompounds, for example, purines or pyrimidines, are sufficient to beable to substitute for them in the anabolic nucleotide pathways. Theseanalogs can then be substituted into the DNA and RNA instead of theirnormal counterparts. The antimetabolites useful herein include: folateantagonists such as methotrexate and trimetrexate pyrimidineantagonists, such as fluorouracil, fluorodeoxyuridine, CB3717,azacytidine, cytarabine, and floxuridine purine antagonists includemercaptopurine, 6-thioguanine, fludarabine, pentostatin; sugar modifiedanalogs include cyctrabine, fludarabine; ribonucleotide reductaseinhibitors include hydroxyurea. Tubulin interactive agents act bybinding to specific sites on tubulin, a protein that polymerizes to formcellular microtubules. Microtubules are critical cell structure units.When the interactive agents bind on the protein, the cell cannot formmicrotubules tubulin interactive agents including vincristine andvinblastine, both alkaloids and paclitaxel.

Hormonal agents are also useful in the treatment of cancers and tumors.They are used in hormonally susceptible tumors and are usually derivedfrom natural sources. These include: estrogens, conjugated estrogens andethinyl estradiol and diethylstilbestrol, chlorotrianisene andidenestrol; progestins such as hydroxyprogesterone caproate,medroxyprogesterone, and megestrol; androgens such as testosterone,testosterone propionate; fluoxymesterone, methyltestosterone; adrenalcorticosteroids are derived from natural adrenal cortisol orhydrocortisone. They are used because of their anti-inflammatorybenefits as well as the ability of some to inhibit mitotic divisions andto halt DNA synthesis. These compounds include prednisone,dexamethasone, methylprednisolone, and prednisolone.

Hormone-related agents include, but are not limited to, leutinizinghormone releasing hormone agents, gonadotropin-releasing hormoneantagonists and anti-hormonal agents. Gonadotropin-releasing hormoneantagonists include leuprolide acetate and goserelin acetate. Theyprevent the biosynthesis of steroids in the testes and are usedprimarily for the treatment of prostate cancer.

Antihormonal agents include antiestrogenic agents such as tamosifen,antiandrogen agents such as Flutamide; and antiadrenal agents such asmitotane and aminoglutethimide. Hydroxyurea appears to act primarilythrough inhibition of the enzyme ribonucleotide reductase. Asparaginaseis an enzyme that converts asparagine to nonfunctional aspartic acid andthus blocks protein synthesis in the tumor.

Gene transfer vectors are capable of introducing a polynucleotide into acell. The polynucleotide may contain the coding sequence of a protein ora peptide, or a nucleotide sequence that encodes a iRNA or antisenseRNA. Examples of gene transfer vectors include, but are not limited to,non-viral vectors and viral vectors. Non-viral vectors typically includea plasmid having a circular double stranded DNA into which additionalDNA segments can be introduced. The non-viral vector may be in the formof naked DNA, polycationic condensed DNA linked or unlinked toinactivated virus, ligand linked DNA, and liposome-DNA conjugates. Viralvectors include, but are not limited to, retrovirus, adenovirus,adeno-associated virus (AAV), herpesvirus, and alphavirus vectors. Theviral vectors can also be astrovirus, coronavirus, orthomyxovirus,papovavirus, paramyxovirus, parvovirus, picomavirus, poxvirus, ortogavirus vectors.

The non-viral and viral vectors also include one or more regulatorysequences operably linked to the polynucleotide being expressed. Anucleotide sequence is “operably linked” to another nucleotide sequenceif the two sequences are placed into a functional relationship. Forexample, a coding sequence is operably linked to a 5′ regulatorysequence if the 5′ regulatory sequence can initiate transcription of thecoding sequence in an in vitro transcription/translation system or in ahost cell. “Operably linked” does not require that the DNA sequencesbeing linked are contiguous to each other. Intervening sequences mayexist between two operably linked sequences.

In one embodiment, the gene transfer vector encodes a short interferingRNA (siRNA). siRNAs are dsRNAs having 19-25 nucleotides. siRNAs can beproduced endogenously by degradation of longer dsRNA molecules by anRNase III-related nuclease called Dicer. siRNAs can also be introducedinto a cell exogenously or by transcription of an expression construct.Once formed, the siRNAs assemble with protein components intoendoribonuclease-containing complexes known as RNA-induced silencingcomplexes (RISCs). An ATP-generated unwinding of the siRNA activates theRISCs, which in turn target the complementary mRNA transcript byWatson-Crick base-pairing, thereby cleaving and destroying the mRNA.Cleavage of the mRNA takes place near the middle of the region bound bythe siRNA strand. This sequence specific mRNA degradation results ingene silencing. In another embodiment, the gene transfer vector encodesan antisense RNA.

Examples of cells include, but are not limited to, stem cells or otherharvested cells.

Manufacture of Stent

The stent body and surface channels can be laser cut, water jet cut,extruded, stamped, molded, lathed or formed. In one embodiment, thestent is cut from a single polymer tube that may be extruded. The tubemay be hollow or the center may be cored out at varying diameterssuitable for the particular indication.

The stent is then etched and is formed on a suitable shaping device togive the stent the desired external geometry. Both the synthetic collartechniques and in vitro valuation techniques show the remarkable abilityof stents of the present application to convert acting force intodeformation work absorbed by the angled structure, which preventsexcessive scaffolding stress, premature material fatigue and acceleratedobsolescence.

The stent of the present application may be formed in such a way as toallow fluid flow to change in the pitch of the flow to improve flowdynamics and to speed the flow of fluids throughout the device. From atight radial design to a more longitudinal design.

In one embodiment spiral surface channels with large cross-section areasare formed to accommodate large volumes of body fluid. In anotherembodiment, multiple channels with small cross-section area are formedto accommodate large volumes of body fluid. In another embodiment, thestent body contains a large center lumen to allow for fluid flow and aplurality of small cross-section area channels on the surface tostabilize the stent in vivo.

In another embodiment, the lips of the channel walls are taped toincrease the surface area for fluid flow and grip. Changes in the depthof the pitch of the channels will also have an impact on fluid flow andstability.

In one embodiment, the stent is formed on a shaping tool that hassubstantially the desired contour of the external stent dimensions. Inthe event the stent is to be shaped to the dimensions of a particularlumen, optical photography and/or optical videography of the targetlumen may be conducted prior to stent formation. The geometry ofcorresponding zones and connector regions of the stent then can beetched and formed in accordance with the requirements of that targetlumen. In particular, if the topography of the biliary duct of aparticular patient is captured optically and the appropriate dimensionprovided, a patient specific prosthesis can be engineered. Thesetechniques can be adapted to other non-vascular lumens but is very wellsuited for vascular applications where patient specific topography is afunction of a variety of factors such as genetics, lifestyle, etc.

Unlike stents made from shape memory metals, the stents of the presentapplication can take on an infinite number of characteristiccombinations as zones and segments within a zone can be modified bychanging angles, segment lengths, segment thicknesses, pitch during theetching and forming stages of stent engineering or during post formationprocessing and polishing steps. Moreover, by modifying the geometry,depth, and diameter of the channels between zones, additionalfunctionality may be achieved, such as flexibility, increased fluidtransport, and changes in friction.

Use of Stent

A stent of the present application is used to support a target site in avessel, duct or lumen and optimize the flow of bodily fluids in asubject in need thereof. Following identification of the target site, anentry portal is established into a vessel, duct or lumen leading to thetarget site. A guide wire is advanced through the entry portal andvessel, duct or lumen to or through the target site. The stent is thenpushed along the guide wire until it reaches the target site and isemplaced there, followed by the withdrawal of the guide wire.

Kit

Another aspect of the present application relates to a kit. The kitcomprises at least one stent of the present application. In someembodiments, the kit further comprises a guide wire for emplacing thestent at a target location. In some embodiments, the kit furthercomprises a pushing catheter for moving the stent along the guide wire.In some embodiments, the kit comprises an introducer sheath orintroducer tube. In some embodiments, the kit further comprises acannula. In some embodiments, the kit further comprises asphincterotome. In some embodiments, the kit comprises a radio-opaquedye.

Example 1: Endoscopic Retrograde Cholangio-Pancreatography (ERCP)

In a subject in need thereof, ECRP is a procedure performed to diagnoseand treat diseases of the gallbladder, bile system, pancreas and liver.

An endoscope is passed though the mouth of the subject down through thestomach and into the duodenum, where the location of the entry of thebile duct into the small intestine is identified. The scope has aworking channel (WC) through which a cannula (catheter) is fed and apractitioner “cannulates” the bile duct (to introduce the cannula intothe bile duct). A guidewire is sent thru the center lumen of the cannulaand is passed thru the bile duct and into the liver. The cannula isremoved and a sphincterotome is introduced. A practitioner cuts thepapilla (the sphincter into bile duct) with the sphincterotome and thesphincterotome is withdrawn. An absorbable polymer stent as describedherein is placed over the guide wire and pushed into the bile duct witha pushing catheter, allowing proper drainage through the bile duct.Depending upon the need of the subject, the stent is made of afast-absorbing polymer, medium-absorbing polymer or slow-absorbingpolymer. The pushing catheter and guidewire are withdrawn from thesubject.

The above description is for the purpose of teaching the person ofordinary skill in the art how to practice the present application, andit is not intended to detail all those obvious modifications andvariations of it which will become apparent to the skilled worker uponreading the description. It is intended, however, that all such obviousmodifications and variations be included within the scope of the presentapplication, which is defined by the following claims. The claims areintended to cover the claimed components and steps in any sequence whichis effective to meet the objectives there intended, unless the contextspecifically indicates the contrary.

What is claimed is:
 1. A stent comprising: an elongated body having a proximal end, a distal end, at least one open spiral channel formed on the exterior surface of said body to provide fluid communication between said proximal end and said distal end, and a central lumen open at the proximal and distal ends of the stent for the passage of a guide wire, wherein the central lumen has a circular, oval or elliptical cross-section and is not in fluid communication with the open spiral channel.
 2. The stent of claim 1, wherein the body is composed of a bioabsorbable polymer.
 3. The stent of claim 1, wherein said at least one open spiral channel has a rotation rate of between about 1.5 and 2.5 twists per inch.
 4. The stent of claim 1, wherein said at least one open spiral channel has a rotation rate of at least about 2 twists per inch.
 5. The stent of claim 1, comprising two open spiral channels formed on the exterior surface of said body.
 6. The stent of claim 5, wherein said channels are on opposite sides on the exterior surface of said body.
 7. The stent of claim 1, wherein said body further comprises an anti-migration device.
 8. The stent of claim 1, wherein said body further comprises a biological agent.
 9. The stent of claim 8, wherein said biological agent is selected from the group consisting of chemotherapeutic agents, antimicrobial agents and gene transfer agents.
 10. The stent of claim 1, wherein said stent has a pre-implantation diameter (D_(pre)) and is in situ expandable upon absorption of a body fluid to a post-implantation diameter (D_(post)), wherein D_(post) is greater than D_(pre).
 11. The stent of claim 1, further comprising a radio-opaque substance.
 12. The stent of claim 1, wherein the open spiral channels are formed integrally on the exterior surface of the elongated body, and wherein the central lumen has a circular cross-section.
 13. A stent comprising: an elongated body composed of a bioabsorbable polymer and having a proximal end, a distal end, at least one open spiral channel formed on the exterior surface of said body to provide fluid communication between said proximal end and said distal end, wherein said at least one open spiral channel has a rotation rate of at least 1 twist per inch, and a central lumen open at the proximal and distal ends of the stent for the passage of a guide wire, wherein the central lumen has a circular, oval or elliptical cross-section and is not in fluid communication with the open spiral channel.
 14. The stent of claim 13, wherein said bioabsorbable polymer comprises PEG and p-dioxanone.
 15. The stent of claim 13, wherein said bioabsorbable polymer comprises PPDO.
 16. The stent of claim 13, wherein said bioabsorbable polymer comprises PLA, trimethylene carbonate and caprolactone.
 17. The stent of claim 13, wherein said at least one open spiral channel has a rotation rate of at least about 2 twists per inch.
 18. The stent of claim 13, comprising two open spiral channels formed on the exterior surface of said body.
 19. The stent of claim 18, wherein said channels are on opposite sides on the exterior surface of said body.
 20. A stent comprising: an elongated body having a proximal end, a distal end, at least one open spiral channel formed on the exterior surface of said body to provide fluid communication between said proximal end and said distal end, wherein said at least one open spiral channel has a rotation rate of between about 1.5 and 3.5 twists per inch, and a central lumen open at the proximal and distal ends of the stent for the passage of a guide wire, wherein the central lumen has a circular, oval or elliptical cross-section and is not in fluid communication with the open spiral channel.
 21. The stent of claim 20, comprising two open spiral channels formed on the exterior surface of said body.
 22. The stent of claim 21, wherein said channels are on opposite sides on the exterior surface of said body.
 23. A stent comprising: an elongated body composed of a bioabsorbable polymer and having a proximal end, a distal end, a pair of open spiral channels formed on the exterior surface of said body to provide fluid communication between said proximal end and said distal end, wherein said spiral channels have a rotation rate of at least about 1 twist per inch, and a central lumen open at the proximal and distal ends of the stent for the passage of a guide wire, wherein the central lumen has a circular, oval or elliptical cross-section and is not in fluid communication with the open spiral channels.
 24. The stent of claim 23, wherein said channels are on opposite sides on the exterior surface of said body. 